Prolonged response to cyclosporin-A in hypoplastic refractory anemia and correlation with in vitro studies

Background and Objectives. Lymphocyte abnormalities in myelodysplastic synd romes (MDS) have been widely described, but the role of the immune system i n the pathogenesis of these clonal disorders remains controversial. An acti ve role of lymphocytes in suppressing normal hematopoiesis may be implicate d in MDS with hypoplastic marrow. We have studied in vitro and in vivo acti vity of cyclosporin-A (CSA) on hematopoiesis in patients affected by hypopl astic MDS without blast excess. Design and Methods. Nine consecutive patients with hypoplastic refractory a nemia (RA), followed up in our out-patient unit, were treated with CSA at d aily doses of 1-3 mg/kg for at least three months. Low dose steroids or dan azol were transiently added in 7/9 patients. Differences between pre- and p osttreatment parameters were studied by the Student's t-test. In vitro effe ct of CSA on circulating hematopoietic progenitors was studied by the methy lcellulose colony assay. Results. Before treatment, fewer circulating hematopoietic progenitors were found in all patients as compared to normal subjects. The number of CD34() cells was about halved, while circulating erythroid and myeloid colony-fo rming cells (CFC) were reduced to one-fifth. After a mean period of 22 mont hs of CSA treatment (median: 14.5 months), hemoglobin was significantly and persistently increased in two patients, platelets in one, platelets and he moglobin in two. Two patients showed transient responses, one patient did n ot tolerate the treatment and one patient is close to a significant respons e. At in vitro CSA concentrations similar to those achieved in vivo after o ral administration the drug significantly increased cell colony growth in h ypoplastic RA. This test correctly predicted a positive clinical response t o CSA in 3/5 cases and treatment failure in 4/4 cases. Interpretation and Conclusions. About one half of hypoplastic RA patients b enefited from CSA treatment. A larger study could verify whether in vitro c ulture of hematopoietic progenitors in the presence of CSA can predict the clinical response and whether this treatment could prolong patients' surviv al. (C) 2000, Ferrata Storti Foundation.